Collection

Glial Cells in Health and Disease

  • Nature | Article

    A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.

    • Shane A. Liddelow
    • , Kevin A. Guttenplan
    • , Laura E. Clarke
    • , Frederick C. Bennett
    • , Christopher J. Bohlen
    • , Lucas Schirmer
    • , Mariko L. Bennett
    • , Alexandra E. Münch
    • , Won-Suk Chung
    • , Todd C. Peterson
    • , Daniel K. Wilton
    • , Arnaud Frouin
    • , Brooke A. Napier
    • , Nikhil Panicker
    • , Manoj Kumar
    • , Marion S. Buckwalter
    • , David H. Rowitch
    • , Valina L. Dawson
    • , Ted M. Dawson
    • , Beth Stevens
    •  &  Ben A. Barres
  • Nature Neuroscience | Resource

    Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice.

    • Thais F Galatro
    • , Inge R Holtman
    • , Antonio M Lerario
    • , Ilia D Vainchtein
    • , Nieske Brouwer
    • , Paula R Sola
    • , Mariana M Veras
    • , Tulio F Pereira
    • , Renata E P Leite
    • , Thomas Möller
    • , Paul D Wes
    • , Mari C Sogayar
    • , Jon D Laman
    • , Wilfred den Dunnen
    • , Carlos A Pasqualucci
    • , Sueli M Oba-Shinjo
    • , Erik W G M Boddeke
    • , Suely K N Marie
    •  &  Bart J L Eggen
  • Nature Immunology | Article

    Microglia are CNS-resident macrophages, but studying their functions in health and disease has been challenging due to a lack of specific markers. Greter and colleagues identify the transcription factor Sall1 as being uniquely associated with microglia in the CNS, where it is important for defining their fate and homeostatic function.

    • Anne Buttgereit
    • , Iva Lelios
    • , Xueyang Yu
    • , Melissa Vrohlings
    • , Natalie R Krakoski
    • , Emmanuel L Gautier
    • , Ryuichi Nishinakamura
    • , Burkhard Becher
    •  &  Melanie Greter
  • Nature Medicine | Article

    μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

    • Gregory Corder
    • , Vivianne L Tawfik
    • , Dong Wang
    • , Elizabeth I Sypek
    • , Sarah A Low
    • , Jasmine R Dickinson
    • , Chaudy Sotoudeh
    • , J David Clark
    • , Ben A Barres
    • , Christopher J Bohlen
    •  &  Grégory Scherrer
  • Nature Communications | Article | open

    The contribution of glia to Huntington's disease is unclear. The authors show that human glial progenitor cells (GPCs) expressing mutant huntingtin impair motor performance when engrafted into wild type mice, and wild type human GPCs ameliorate disease phenotypes when engrafted into an HD mouse model.

    • Abdellatif Benraiss
    • , Su Wang
    • , Stephanie Herrlinger
    • , Xiaojie Li
    • , Devin Chandler-Militello
    • , Joseph Mauceri
    • , Hayley B. Burm
    • , Michael Toner
    • , Mikhail Osipovitch
    • , Qiwu Jim Xu
    • , Fengfei Ding
    • , Fushun Wang
    • , Ning Kang
    • , Jian Kang
    • , Paul C. Curtin
    • , Daniela Brunner
    • , Martha S. Windrem
    • , Ignacio Munoz-Sanjuan
    • , Maiken Nedergaard
    •  &  Steven A. Goldman
  • Nature | Letter

    In a mouse model of ischaemia, mitochondrial particles released from astroctyes are taken up by adjacent neurons, leading to enhanced cell survival signalling; disruption of this release mechanism resulted in worsened neurological outcomes.

    • Kazuhide Hayakawa
    • , Elga Esposito
    • , Xiaohua Wang
    • , Yasukazu Terasaki
    • , Yi Liu
    • , Changhong Xing
    • , Xunming Ji
    •  &  Eng H. Lo
  • Nature | Letter

    Neurotrophic factors produced by enteric glia in response to microbiota and alarmin cues regulate IL-22 production by group 3 innate lymphoid cells in the gut; disruption of this pathway leads to impaired clearance of Citrobacter rodentium and defects in epithelial integrity in a model of intestinal inflammation.

    • Sales Ibiza
    • , Bethania García-Cassani
    • , Hélder Ribeiro
    • , Tânia Carvalho
    • , Luís Almeida
    • , Rute Marques
    • , Ana M. Misic
    • , Casey Bartow-McKenney
    • , Denise M. Larson
    • , William J. Pavan
    • , Gérard Eberl
    • , Elizabeth A. Grice
    •  &  Henrique Veiga-Fernandes
  • Nature | Article

    A heterotypic cell interaction between astrocytes and tumour cells colonizing the brain is discovered; by establishing gap junctions, tumour cells trigger the activation of innate immune response signalling in astrocytes, which results in the secretion of factors that support growth and chemoresistance in brain metastatic cells.

    • Qing Chen
    • , Adrienne Boire
    • , Xin Jin
    • , Manuel Valiente
    • , Ekrem Emrah Er
    • , Alejandro Lopez-Soto
    • , Leni S. Jacob
    • , Ruzeen Patwa
    • , Hardik Shah
    • , Ke Xu
    • , Justin R. Cross
    •  &  Joan Massagué
  • Nature | Article

    Mouse models of Alzheimer’s disease show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline; driving neurons to oscillate at gamma frequency (40 Hz) reduces levels of amyloid-β peptides.

    • Hannah F. Iaccarino
    • , Annabelle C. Singer
    • , Anthony J. Martorell
    • , Andrii Rudenko
    • , Fan Gao
    • , Tyler Z. Gillingham
    • , Hansruedi Mathys
    • , Jinsoo Seo
    • , Oleg Kritskiy
    • , Fatema Abdurrob
    • , Chinnakkaruppan Adaikkan
    • , Rebecca G. Canter
    • , Richard Rueda
    • , Emery N. Brown
    • , Edward S. Boyden
    •  &  Li-Huei Tsai
  • Nature | Letter

    A single sentence summarizing your paper (websum), which will appear online on the table of contents and in e-alerts, has been provided below. Please check this sentence for accuracy and appropriate emphasis.

    • Itay Tirosh
    • , Andrew S. Venteicher
    • , Christine Hebert
    • , Leah E. Escalante
    • , Anoop P. Patel
    • , Keren Yizhak
    • , Jonathan M. Fisher
    • , Christopher Rodman
    • , Christopher Mount
    • , Mariella G. Filbin
    • , Cyril Neftel
    • , Niyati Desai
    • , Jackson Nyman
    • , Benjamin Izar
    • , Christina C. Luo
    • , Joshua M. Francis
    • , Aanand A. Patel
    • , Maristela L. Onozato
    • , Nicolo Riggi
    • , Kenneth J. Livak
    • , Dave Gennert
    • , Rahul Satija
    • , Brian V. Nahed
    • , William T. Curry
    • , Robert L. Martuza
    • , Ravindra Mylvaganam
    • , A. John Iafrate
    • , Matthew P. Frosch
    • , Todd R. Golub
    • , Miguel N. Rivera
    • , Gad Getz
    • , Orit Rozenblatt-Rosen
    • , Daniel P. Cahill
    • , Michelle Monje
    • , Bradley E. Bernstein
    • , David N. Louis
    • , Aviv Regev
    •  &  Mario L. Suvà
  • Nature | Letter

    People infected with West Nile virus often experience cognitive side effects including memory loss through unknown mechanisms; mice and humans infected with the virus experience a loss in hippocampal presynaptic terminals, which can be reversed by disrupting complement or microglia in mice.

    • Michael J. Vasek
    • , Charise Garber
    • , Denise Dorsey
    • , Douglas M. Durrant
    • , Bryan Bollman
    • , Allison Soung
    • , Jinsheng Yu
    • , Carlos Perez-Torres
    • , Arnaud Frouin
    • , Daniel K. Wilton
    • , Kristen Funk
    • , Bette K. DeMasters
    • , Xiaoping Jiang
    • , James R. Bowen
    • , Steven Mennerick
    • , John K. Robinson
    • , Joel R. Garbow
    • , Kenneth L. Tyler
    • , Mehul S. Suthar
    • , Robert E. Schmidt
    • , Beth Stevens
    •  &  Robyn S. Klein
  • Nature | Letter

    Microglial phagocytosis is required for neurogenic niche maintenance and response to injury; the TAM kinases Mer and Axl are expressed by microglia in the adult CNS, and mediate the clearance of apoptotic cells from the niche.

    • Lawrence Fourgeaud
    • , Paqui G. Través
    • , Yusuf Tufail
    • , Humberto Leal-Bailey
    • , Erin D. Lew
    • , Patrick G. Burrola
    • , Perri Callaway
    • , Anna Zagórska
    • , Carla V. Rothlin
    • , Axel Nimmerjahn
    •  &  Greg Lemke
  • Nature | Article

    Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.

    • Mark A. Anderson
    • , Joshua E. Burda
    • , Yilong Ren
    • , Yan Ao
    • , Timothy M. O’Shea
    • , Riki Kawaguchi
    • , Giovanni Coppola
    • , Baljit S. Khakh
    • , Timothy J. Deming
    •  &  Michael V. Sofroniew
  • Nature Neuroscience | Article

    The acquisition of a new skill or motor program is thought to be mediated by changes in neuronal plasticity at early stages of learning, which is later stabilized by new myelin generated by oligodendrocytes. In this study, the authors show that oligodendrocyte precursors exist in a ‘primed’ state, which allows them to contribute to early stages of motor learning.

    • Lin Xiao
    • , David Ohayon
    • , Ian A McKenzie
    • , Alexander Sinclair-Wilson
    • , Jordan L Wright
    • , Alexander D Fudge
    • , Ben Emery
    • , Huiliang Li
    •  &  William D Richardson
  • Nature Neuroscience | Article

    The nature of astrocyte diversity in the adult brain has remained poorly defined. The authors identify five astrocyte subpopulations in the brain that exhibit extensive molecular and functional diversity. They uncover correlative populations in malignant glioma, providing insight into how diverse astrocyte populations contribute to synaptogenesis, tumor pathophysiology and neurological disease.

    • Chia-Ching John Lin
    • , Kwanha Yu
    • , Asante Hatcher
    • , Teng-Wei Huang
    • , Hyun Kyoung Lee
    • , Jeffrey Carlson
    • , Matthew C Weston
    • , Fengju Chen
    • , Yiqun Zhang
    • , Wenyi Zhu
    • , Carrie A Mohila
    • , Nabil Ahmed
    • , Akash J Patel
    • , Benjamin R Arenkiel
    • , Jeffrey L Noebels
    • , Chad J Creighton
    •  &  Benjamin Deneen
  • Nature Neuroscience | Article

    Neocortical resident microglia are long-lived cells. Füger et al. report that approximately half of these cells survive for the entire lifespan of a mouse. While microglial proliferation under homeostatic conditions is low, proliferation is increased in a mouse model of Alzheimer's disease.

    • Petra Füger
    • , Jasmin K Hefendehl
    • , Karthik Veeraraghavalu
    • , Ann-Christin Wendeln
    • , Christine Schlosser
    • , Ulrike Obermüller
    • , Bettina M Wegenast-Braun
    • , Jonas J Neher
    • , Peter Martus
    • , Shinichi Kohsaka
    • , Martin Thunemann
    • , Robert Feil
    • , Sangram S Sisodia
    • , Angelos Skodras
    •  &  Mathias Jucker
  • Nature Immunology | Article

    Microglia are the tissue-resident macrophages of the brain. Ouyang and colleagues show the ER-resident transmembrane protein NRROS is necessary for proper development and function of microglia. Mice lacking NRROS exhibit neurologic defects and die prematurely.

    • Kit Wong
    • , Rajkumar Noubade
    • , Paolo Manzanillo
    • , Naruhisa Ota
    • , Oded Foreman
    • , Jason A Hackney
    • , Brad A Friedman
    • , Rajita Pappu
    • , Kimberly Scearce-Levie
    •  &  Wenjun Ouyang
  • Nature Immunology | Article

    Gliomas recruit and manipulate microglial function to promote their growth. Joseph and colleagues reveal the molecular basis of this manipulation by showing that gliomas trigger S-nitrosylation of microglial caspase-3 and thereby initiate a tumor-promoting phenotype.

    • Xianli Shen
    • , Miguel A Burguillos
    • , Ahmed M Osman
    • , Jeroen Frijhoff
    • , Alejandro Carrillo-Jiménez
    • , Sachie Kanatani
    • , Martin Augsten
    • , Dalel Saidi
    • , Johanna Rodhe
    • , Edel Kavanagh
    • , Anthony Rongvaux
    • , Vilma Rraklli
    • , Ulrika Nyman
    • , Johan Holmberg
    • , Arne Östman
    • , Richard A Flavell
    • , Antonio Barragan
    • , Jose Luis Venero
    • , Klas Blomgren
    •  &  Bertrand Joseph
  • Nature Immunology | Article

    Microglia progenitors seed the central nervous system from the yolk sac, but little is known about the origin of non-parenchymal macrophages. Prinz and colleagues demonstrate that these macrophages in the central nervous system are related to but distinct from microglia and are largely of embryonic origin.

    • Tobias Goldmann
    • , Peter Wieghofer
    • , Marta Joana Costa Jordão
    • , Fabiola Prutek
    • , Nora Hagemeyer
    • , Kathrin Frenzel
    • , Lukas Amann
    • , Ori Staszewski
    • , Katrin Kierdorf
    • , Martin Krueger
    • , Giuseppe Locatelli
    • , Hannah Hochgerner
    • , Robert Zeiser
    • , Slava Epelman
    • , Frederic Geissmann
    • , Josef Priller
    • , Fabio M V Rossi
    • , Ingo Bechmann
    • , Martin Kerschensteiner
    • , Sten Linnarsson
    • , Steffen Jung
    •  &  Marco Prinz
  • Nature Medicine | Letter

    The release of ATP from spinal microglia via pannexin-1 channels is required for withdrawal symptoms after termination of chronic opioid treatment in rodents, and pharmacological blockade of pannexin-1 channels reduces the severity of withdrawal without affecting opiate analgesia.

    • Nicole E Burma
    • , Robert P Bonin
    • , Heather Leduc-Pessah
    • , Corey Baimel
    • , Zoe F Cairncross
    • , Michael Mousseau
    • , Jhenkruthi Vijaya Shankara
    • , Patrick L Stemkowski
    • , Dinara Baimoukhametova
    • , Jaideep S Bains
    • , Michael C Antle
    • , Gerald W Zamponi
    • , Catherine M Cahill
    • , Stephanie L Borgland
    • , Yves De Koninck
    •  &  Tuan Trang
  • Nature Medicine | Article

    After upregulation of AHR in astrocytes by type I interferons, commensal-microbe-derived metabolites of dietary tryptophan act on astrocytes to suppress CNS inflammation.

    • Veit Rothhammer
    • , Ivan D Mascanfroni
    • , Lukas Bunse
    • , Maisa C Takenaka
    • , Jessica E Kenison
    • , Lior Mayo
    • , Chun-Cheih Chao
    • , Bonny Patel
    • , Raymond Yan
    • , Manon Blain
    • , Jorge I Alvarez
    • , Hania Kébir
    • , Niroshana Anandasabapathy
    • , Guillermo Izquierdo
    • , Steffen Jung
    • , Nikolaus Obholzer
    • , Nathalie Pochet
    • , Clary B Clish
    • , Marco Prinz
    • , Alexandre Prat
    • , Jack Antel
    •  &  Francisco J Quintana
  • Nature Medicine | Letter

    In response to signals from afferent TRPV1+ C-fibers, STAT3-dependent upregulation of LCN2 in reactive astrocytes of the spinal dorsal horn amplifies itch signaling in multiple rodent models of atopic and contact dermatitis.

    • Miho Shiratori-Hayashi
    • , Keisuke Koga
    • , Hidetoshi Tozaki-Saitoh
    • , Yuta Kohro
    • , Honami Toyonaga
    • , Chiharu Yamaguchi
    • , Ayumi Hasegawa
    • , Takeshi Nakahara
    • , Junichi Hachisuka
    • , Shizuo Akira
    • , Hideyuki Okano
    • , Masutaka Furue
    • , Kazuhide Inoue
    •  &  Makoto Tsuda
  • Nature Medicine | Article

    In a mouse model of spinal cord injury, reactive astrogliosis is found to be context dependent and reversible. Blockade of type I collagen–reactive astrocyte interactions prevents astrocyte scar formation and facilitates functional recovery after injury.

    • Masamitsu Hara
    • , Kazu Kobayakawa
    • , Yasuyuki Ohkawa
    • , Hiromi Kumamaru
    • , Kazuya Yokota
    • , Takeyuki Saito
    • , Ken Kijima
    • , Shingo Yoshizaki
    • , Katsumi Harimaya
    • , Yasuharu Nakashima
    •  &  Seiji Okada
  • Nature Communications | Article | open

    How microglia contribute to brain injury or repair is unclear. Here combining microglia manipulations and calcium imaging, the authors show that selective elimination of microglia leads to disrupted neuronal calcium dynamics and markedly increased brain injury after cerebral ischemia.

    • Gergely Szalay
    • , Bernadett Martinecz
    • , Nikolett Lénárt
    • , Zsuzsanna Környei
    • , Barbara Orsolits
    • , Linda Judák
    • , Eszter Császár
    • , Rebeka Fekete
    • , Brian L. West
    • , Gergely Katona
    • , Balázs Rózsa
    •  &  Ádám Dénes
  • Nature Communications | Article | open

    Core clock genes, such as Bmal1, are expressed in astrocytes, but their contribution to the timekeeping system is unknown. Barca-Mayo et al. report that deletion of Bmal1 in Glast+ astrocytes alters the neuronal clock through GABA signalling, leading to abnormal circadian locomotor behaviour and impaired cognition in mice.

    • Olga Barca-Mayo
    • , Meritxell Pons-Espinal
    • , Philipp Follert
    • , Andrea Armirotti
    • , Luca Berdondini
    •  &  Davide De Pietri Tonelli
  • Nature Communications | Article | open

    While transcranical direct current stimulation (tDCS) is used in clinical setting, its cellular mechanism of action is unclear. Here, Hajime Hirase and colleagues visualize cellular response in mouse brain to tDCS and show robust astrocyte activation that coincide with plasticity changes.

    • Hiromu Monai
    • , Masamichi Ohkura
    • , Mika Tanaka
    • , Yuki Oe
    • , Ayumu Konno
    • , Hirokazu Hirai
    • , Katsuhiko Mikoshiba
    • , Shigeyoshi Itohara
    • , Junichi Nakai
    • , Youichi Iwai
    •  &  Hajime Hirase
  • Nature Communications | Article | open

    Microglia and monocytes contribute to neuropathic pain states, but the precise role of the two cell types is not clear. Here Peng et al. use temporally controlled ablation of monocytes and microglia in mice to show that these cells work together to initiate neuropathic-pain like behaviour, but are less important in the maintenance phase.

    • Jiyun Peng
    • , Nan Gu
    • , Lijun Zhou
    • , Ukpong B Eyo
    • , Madhuvika Murugan
    • , Wen-Biao Gan
    •  &  Long-Jun Wu
  • Nature Communications | Article | open

    How neurons and neuronal activity regulate astrocyte functions is poorly understood. Hasel et al. identify two large groups of astrocytic genes that are regulated by neuronal contact and synaptic activity respectively, with distinct roles in astrocytic function; interestingly, many of these genes are dysregulated in neurodegeneration.

    • Philip Hasel
    • , Owen Dando
    • , Zoeb Jiwaji
    • , Paul Baxter
    • , Alison C. Todd
    • , Samuel Heron
    • , Nóra M. Márkus
    • , Jamie McQueen
    • , David W. Hampton
    • , Megan Torvell
    • , Sachin S. Tiwari
    • , Sean McKay
    • , Abel Eraso-Pichot
    • , Antonio Zorzano
    • , Roser Masgrau
    • , Elena Galea
    • , Siddharthan Chandran
    • , David J. A. Wyllie
    • , T. Ian Simpson
    •  &  Giles E. Hardingham
  • Nature Communications | Article | open

    Glial scars are thought to provide a biochemical and mechanical barrier to neuronal regeneration post-injury, but the mechanical properties of the scars have not been studied in detail. Here the authors perform atomic force microscopy measurements of glial scars from the injured rat cortex and spinal cord, and find that brain tissue softens in response to the injury.

    • Emad Moeendarbary
    • , Isabell P. Weber
    • , Graham K. Sheridan
    • , David E. Koser
    • , Sara Soleman
    • , Barbara Haenzi
    • , Elizabeth J. Bradbury
    • , James Fawcett
    •  &  Kristian Franze
  • Nature Communications | Article | open

    Hidden hearing loss (HHL) is an auditory neuropathy that impairs one’s ability to hear, particularly in a noisy environment. Here the authors show that in mice, transient loss of cochlear Schwann cells results in permanent disruption of the cochlear heminodal structure, leading to auditory deficits characteristic of HHL.

    • Guoqiang Wan
    •  &  Gabriel Corfas